Emerging evidence points to coordinated action of chemical and mechanical cues during brain development. At early stages of neocortical development, angiogenic factors and chemokines such as CXCL12, ephrins, and semaphorins assume crucial roles in orchestrating neuronal migration and axon elongation of postmitotic neurons. Here we explore the intrinsic mechanical properties of the developing marginal zone of the pallium in the migratory pathways and brain distribution of the pioneer Cajal-Retzius cells. These neurons are generated in several proliferative regions in the developing brain (e.g., the cortical hem and the pallial subpallial boundary) and migrate tangentially in the preplate/marginal zone covering the upper portion of the developing cortex. These cells play crucial roles in correct neocortical layer formation by secreting several molecules such as Reelin. Our results indicate that the motogenic properties of Cajal-Retzius cells and their perinatal distribution in the marginal zone are modulated by both chemical and mechanical factors, by the specific mechanical properties of Cajal-Retzius cells, and by the differential stiffness of the migratory routes. Indeed, cells originating in the cortical hem display higher migratory capacities than those generated in the pallial subpallial boundary which may be involved in the differential distribution of these cells in the dorsal-lateral axis in the developing marginal zone.
Urrea, L., Segura, Miriam, Masuda-Suzukake, M., Hervera, A., Pedraz, L., Aznar, J. M. G., Vila, M., Samitier, J., Torrents, E., Ferrer, Isidro, Gavín, R., Hagesawa, M., Del Río, J. A., (2018). Involvement of cellular prion protein in α-synuclein transport in neuronsMolecular Neurobiology 55, (3), 1847-1860
The cellular prion protein, encoded by the gene Prnp, has been reported to be a receptor of β-amyloid. Their interaction is mandatory for neurotoxic effects of β-amyloid oligomers. In this study, we aimed to explore whether the cellular prion protein participates in the spreading of α-synuclein. Results demonstrate that Prnp expression is not mandatory for α-synuclein spreading. However, although the pathological spreading of α-synuclein can take place in the absence of Prnp, α-synuclein expanded faster in PrPC-overexpressing mice.
Badiola, M., Hervera, A., López, J., Segura, Miriam, del Río, J. A., Samitier, J., (2017). In-vitro Peripheral Nervous System on a chipCASEIB Proceedings XXXV Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2017) , Sociedad Española de Ingeniería Biomédica (Valencia, Spain) , XXXX (falta pdf)
Understanding the basic mechanisms of neural regeneration after injury is a pre-requisite for developing appropriate treatments. Traditional approaches to model axonal lesions, such as high intensity power laser ablation or sharp metal scratching, are complex to implement, have low throughputs, and generate cuts that are difficult to modulate. We present here a novel reproducible microfluidic approach to model in vitro mechanical lesion of tens to hundreds of axons simultaneously in a controlled manner. The dimensions of the induced axonal injury and its distance from the neuronal cell body are precisely controlled while preserving both the proximal and distal portions of axons. We have observed that distal axons undergo Wallerian-like anterograde degeneration after axotomy; in contrast, proximal portions of the axons remain un-degenerated, possessing the potential to re-grow. More importantly, surpassing the previous axotomy methods performed in Petridishes in which local microenvironments cannot be tailored, our platform holds the capability to implement fine-tuned treatments to lesioned axon stumps in a local, controlled manner. Specifically, molecules such as chondroitin sulphate proteoglycans and its degrading enzyme chondroitinase ABC, hydrogels, and supporting cells have been shown to be deliverable to the lesioned site of injured axons. In addition, this system also permits double interventions at the level of the lesioned axons and the perikaryon. This proves the potential of our model by demonstrating how axonal regrowth can be evaluated under circumstances that are better mimics of biological problems. We believe that this novel mechanical microfluidic axotomy approach is easy to perform, yields high throughput axon lesions, is physiologically relevant, and offers a simplified platform for screening of potential new neurological drugs.
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